The directional preparation of lignin-based pyrimidine derivatives by Dalian Institute of Chemical Physics, etc.

Recently, Zhang Tao, an academician of the Chinese Academy of Sciences and a researcher at the Center for Catalysis and New Materials, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, and Li Changzhi, a researcher, developed a transition metal-free catalytic depolymerization of phenolic β-O-4 lignin model compounds for the directional preparation of pyrimidines.
The new strategy of derivatives opens up a new path for the high-value transformation of lignin to prepare nitrogen-containing heterocyclic pharmaceutical intermediates
.

Obtaining high value-added nitrogen-containing aromatic chemicals through the participation of nitrogen atoms in depolymerization of lignin is a new direction for high-value transformation of lignin
.
At present, most N-involved lignin conversion strategies are limited to the reaction of depolymerized monomers
.
For the main structural fragments of lignin β-O-4, oxidative pretreatment is often required, followed by amination reaction to generate corresponding cyclohexylamine and aromatic amine chemicals
.
The direct conversion of this chemical to nitrogen-containing aromatic heterocyclic compounds is challenging due to the cleavage of CO/CC bonds, the precise construction of CN bonds, and the high coupling of multi-step reactions
.

In this work, with the participation of organic amines, a new strategy for the directional preparation of pyrimidine derivatives by one-pot depolymerization of β-O-4 lignin model compounds was developed, and an analog of the antitumor drug marine alkaloid Meridianin was successfully synthesized
.
Compared with the reported organic synthesis routes, this strategy has cheap and renewable starting materials, simple steps, and greatly improves the overall efficiency and atom economy
.

The research uses β-O-4 model compound, benzamidine and benzyl alcohol as substrates, and uses NaOH to promote a one-pot multi-component series coupling reaction, so as to realize the directional preparation of lignin-based pyrimidine derivatives.
A universal method for the direct conversion of β-O-4 fragments into bio-based pyrimidine derivatives; in cooperation with Professor Lei Ming's research group from Beijing University of Chemical Technology, through a combination of controlled experiments and theoretical calculations, the mechanism of CO bond cleavage and CN bond generation in lignin was elucidated.
The optimal reaction route proved that acetophenones are the main hydrogen acceptors in the dehydrogenation step
.
The system has distinctive features, and is the first reaction system for the directional conversion of the main structural fragments of lignin into pyrimidine derivatives; no external hydrogen source or oxygen source is required, the one-pot series coupling reaction is easy to operate, and the atom economy is high; based on this reaction system , research and synthesis of natural alkaloid Meridianin derivatives, proved its application potential in drug synthesis
.

The team developed a series of catalytic depolymerization strategies in the early stage to realize the directional conversion of lignin into energy chemicals such as phenols, aromatic hydrocarbons, aromatic ketones, benzylamines, and polycyclic alkanes in the jet fuel section (J.
Energy Chem.
, Appl.
Catal.
B: Environ.
, ACS Catal.
, ACS Catal.
, Angew.
Chem.
In.
Ed.
, ChemSusChem.
, ACS Catal.
, Green.
Chem.
, Angew.
Chem.
Int.
Ed.
, Chem.
Sci.
)
.

The related research results, titled Transition-metal-free Synthesis of Pyrimidines from Lignin β-O-4 Segments via a One-pot Multi-component Reaction, were published in Nature Communications
.
The research work is supported by the National Key R&D Program, the National Natural Science Foundation of China, the Chinese Academy of Sciences' Strategic Pilot Science and Technology Project (Type B) "Essence and Regulation of Energy Chemical Conversion", and the International Cooperation Project of the Royal Society of Chemistry
.

The directional preparation of lignin-based pyrimidine derivatives by Dalian Institute of Chemical Physics, etc.